This application proposes a unique and complete research training program consisting of three parts. It starts with basic science research training in the laboratory of Dr. B.R. Duling, is followed by clinical anesthesia training, and then enters a period of transition which will allow me to develop an independent laboratory under the co-sponsorship of Dr. Duling and a clinical microcirculatory investigator, Dr. D.E. Longnecker. The research plan follows similar lines with basic research during phase I and studies of a more applied nature during phase II. The research is based on the fact that endothelium is a significant partner in the vasoactive response of blood vessels, at least the conduit vessels. Now, further studies need to be done to determine if this occurs in the microvessels, how it may be related to the pathophysiology of hypertension, and its role in the autoregulation of tissue blood flow. I hypothesize that the endothelium plays the major role in controlling the response of vascular smooth muscle in arterioles and that it is also the sight of action for autoregulation of blood flow and the peripheral control of blood pressure. During phase I of the program, hamster cheek pouch arterioles will be isolated and cannulated in vitro, and then the relative contributions of the endothelium and vascular smooth muscle to the vasoactive responses will be separated by various experimental approaches. During phase II the endothelium's role in the mechanism of autoregulation and the pathophysiology of hypertension will be investigated. Autoregulation will be studied by monitoring vessel responses to alterations in pressure and flow, either with or without the endothelial function. Hypertension will be studied by comparing the endothelial function in the mesentaric arterioles of SHR and WKY rats using the techniques to be developed in phase I.